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Application of Compounds in Anti-Dengue and Zika Virus Infection
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A virus infection, dengue virus technology, applied in the field of compounds
Active Publication Date: 2020-04-07
TSINGHUA UNIV
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There is currently no specific treatment for Zika virus infection
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Embodiment 1
[0037] Embodiment 1, the preparation of compound 1-94
[0038]
[0039] Get intermediate A1 in 100ml round bottom flask, add 198mg Pd(dppf) 2 .DCM, 2g potassium phosphate and 1.2g p-trifluoromethylthiophenylboronic acid pinacol ester, add 10ml toluene, under the protection of argon, react at 100°C for 12h, spin the solvent, add 100ml water, extract with 20ml dichloromethane Twice, using petroleum ether: ethyl acetate = 30:1 to pass through a silica gel column to obtain 1 g of intermediate A3 (colorless liquid), with a yield of 64%.
[0040] Take 1g of intermediate A3 and 650mg of intermediate A4 in a 25ml round bottom flask, add 240mg of p-toluenesulfonic acid monohydrate and 10ml of n-butanol, react at 130°C for 16h, spin the solvent under reduced pressure, add water, and use 20ml of ethyl acetate Extracted twice, and passed through a silica gel column with ethyl acetate:petroleum ether=1:1 to obtain 320 mg of compound 1 (white solid), with a total yield of 24%.
[0041]...
Embodiment 2
[0044] Embodiment 2, the inhibitory activity of compound to dengue virus and Zika virus
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Abstract
The invention discloses an application of a compound in resisting dengue and zika virus infection. Compounds shown in a formula I, pharmaceutically acceptable salts thereof or prodrugs thereof, can beused for prevention and / or treatment of viral infections, the virus can be a dengue virus or a zika virus, and the dengue virus is a type II dengue virus. Among the compounds shown in the formula I,the compounds shown by a formula II (compounds including 2, 4, 13, 37, 47, 83, 91, 93, 94 and the like) have remarkable inhibitory activity; among these compounds, especially compound 93 has an EC50 value in a range of 20-30nM for the dengue virus and the zika virus, and has an excellent effect. Experiments prove that the compounds shown in the formula I and the pharmaceutically acceptable salts or prodrugs thereof can be used for preventing and / or treating dengue virus or zika virus infection.
Description
technical field [0001] The present invention relates to the application of a compound in resisting dengue and Zika virus infection. Background technique [0002] Dengue virus (Dengue virus) and Zika virus (Zika virus) both belong to the Flavivirus genus of the Flaviviridae. etc.) spread to cause infection and can be classified as "arboviruses". [0003] Dengue viruses are stored in humans and monkeys and are transmitted by Aedes mosquitoes. After the virus infects the human body, it can proliferate in the capillary endothelium and monocytes, and then spread through the bloodstream, causing fever, muscle and joint pain, lymph node swelling, skin bleeding and shock. The clinical symptoms of dengue fever vary in severity. Generally, the first-time infection has mild symptoms and recovers within a week. Re-infected patients have severe symptoms and often have dengue hemorrhage / dengue shock syndrome, and the mortality rate is as high as 5% to 10%. There are currently no effec...
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Application Information
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